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Orthopox is Cryptosporidium's mission officer, who gives him his assignments. Orthopox is known for being both extremely intelligent and extremely prideful, in other words, Orthopox is basically a mad scientist. Despite being gifted with a large brain, Pox's own schemes and plans lack a bit of foresight, not to mention appealing to his ego ensures remaining on Pox's good side.

While Orthopox is indeed capable of inventing new weaponry and upgrades, he usually does it at a price. It's clear Pox is a businessman, having started his own successful fast-food franchise and running Crypto's casino. Pox also shows a bit of a sadistic streak and, much like Crypto, has little regard for life, unless they prove to be strategically valuable. Being a high-ranking Furon Commander, Orthopox is quite bossy and narcissistic. These traits were elevated after Orthopox lost his own body, angering him to no end.

Pox is mostly identified by his labcoat, four large horns protruding from his head, and the two metal links used to hold his head up; a trait not seen in any other Furon. Pox's own head is quite big, marking him as a very high-ranking and intelligent Furon. His incarnation as Orthopox 14 has shrunken his head, and replaced his original, meek body with a much stronger, monkey body.

Nothing is known about Orthopox before the invasion of Earth, except that he was able to conquer quite a few worlds for the Empire, and that he and Crypto have been companions all their lives, being like a father figure toward the Furon soldier. Some of Pox's known military achievements include the conquest of Zarkon-5, being the hero of the Battle of Tharsis Mons, and the winner of the Xanthrax-47 Mental Cruelty Award 6 years running. At one point, he was romantically involved with a female Furon called E. Coli who simply used him and promptly dumped him after she was done with him.

Years before the invasion, Orthopox presented his plan for obtaining Furon DNA to the War Council and sent Crypto 136 to scout Earth for said DNA. After loosing contact with 136, the newly cloned Crypto 137 urges that they go to Earth to rescue his "brother" in peril. In 1959, a Furon Mothership under the command of Orthopox reached to the planet and

Orthopox on the Furon Mothership

search for Crypto 136. Orthopox remained in the mothership, handing out assignments as Crypto infiltrated humanity and selling him upgrades, in exchange for DNA. After 137 discovered that 136 had been killed and dissected, the duo continued to fight humanity in order to avenge Crypto 136 and claim Earth in the name of the Furon Empire. Pox continued to send Crypto on missions, including the disbanding of the Joint Chiefs to prevent them from uniting, the assassination of General Armquist and President Huffman, and the defeat of Silhouette, the leader of the American Majestic branch. With no one left to oppose them, Crypto and Pox claim Earth as a territory of the Furon Empire, though they only managed to gain control of one country. While Crypto posed as the president, Orthopox continued experimentation and managed to use the acquired DNA to restore Crypto's genitalia.

In 1969, Orthopox 13 was killed when a KGB missile destroys the Mothership. However, he was able to download his conscious mind into a HoloPox unit; a Furon hologram projector that was formerly used for long-distance communication. At this point, Orthopox began to interact with humans, mostly as allies, and urged Crypto 138 to avoid becoming fond of them.

Soon after defeating the Soviets and the destruction of the Blisk, Orthopox created the Big Willy's Hot Dog franchise, in which he feeds the grinded up flesh of dead humans in the form of hot dogs, as a way to get rid of the bodies Crypto left behind over the years. Pox also creates the Big Willy mech; a robotic suit disguised as the franchise's mascot and piloted by Crypto to destroy Pox's business rival Colonel Kluckin. During their mission, Pox was fooled into joining Mr. Pork in exchange for gaining a new body. The results were disastrous, leading to Orthopox almost being erased and an all-out attack, resulting in Mr. Pork's death.

By 1979, the Furons had left the fast food business and moved on to run a casino in Las Paradiso. While business was going well, Cypto caught the attention of the Molinari brothers and began a war. After dealing with the Molinari, the Space Dust was attacked by Nexosporidium Warriors. Orthopox then ordered that the city be destroyed; including their casino. The duo then set out to find the conspirators who sent the Nexos after them. The answers were then presented by a Furon known as the Master, who told them that the conspirators came from Furon. Following the death of the Master, their search took a strange turn when they discovered synthetic Furon DNA, {C
which made their mission pointless. In a bout of rage, Crypto left Earth and took Orthopox with him to the Fourth Ring of Furon in order to make Emperor Meningitis pay.

After collaborating with a cloner on the Fourth Ring of Furon, Orthopox obtains a new body, alhtough the cloner picked the wrong body mold and gave him a monkey's body. Orthopox 14 made a few attempts at killing himself in order to escape the humiliation of his new body. He still continued aiding Crypto in his quest to face the Emperor, and helped him break into the palace. After Crypto dispatched the Emperor, the Master appeared before them, revealing that he had tricked Crypto into killing Meningitis and allowing him to take over. However, the Master did not take into account the fact that Crypto would allow Pox to smack the Master into a wall, reducing him to paste.

Following the death of the Emperor and the Master, Crypto had doubts about what to do upon discovering that his mission was a sham. Orthopox managed to motivate Crypto by telling him that there would always be reason to go out and destroy humanity. Orthopox then took a seat at the empty throne, and bid farewell to Crypto, who guaranteed they would meet ten years later. Orthopox was cheered by the masses who rushed into the palace.

"Emperor Meningitis is dead! Long live Emperor Orthopox!

Holy crap! He's a monkey! Primo!
"

―Two Unknown Furon civilians

It is quite probable that Orthopox will make a fixed clone of himself, since he is the emperor.

Having a number of clones as low as 14 (most likely 15 after the events of Path of the Furon), Pox is considered an elder among Furon.

Before the events of Path of the Furon, Pox had built himself a new holopox unit. This new and improved unit not only improved Pox's appearance, but it also had a set of three hands, allowing Pox to grab items and continue his experiments on humans.

Orthopox constantly complained about his status as a non-corporeal being, before being re-cloned.

After Pox was recloned, with his new monkey body, his head was considerably smaller. Allowing him to walk about, without the need of a chair.

When selling Crypto upgrades during Destroy all Humans, if the player tries to buy something without enough DNA `Pox will sometime say "if you don't eat your meat you can't have any pudding", a line from the band Pink Floyd's song, 'Another Brick in the Wall'.

Pox is voiced by Richard Horvitz, who is famous for voicing Zim on the Nickelodeon cartoon Invader ZIM. As such, Pox shares a plethora of qualities with the Irken.